We wish to develop a model of diabetic retinopathy in the laboratory rat, and to deterimine if the abnormalities we expect to produce can be prevented by appropriate treatment. Rats will be made diabetic by streptozotocin administration and, in addition, some groups of animals will either be fed sucrose rich diets or will have systemic hypertension on a genetic basis (SHR strain of albino rat). Therapy will involve either daily administration of insulin or of quercitrin or CP-45,634 (a potent aldose reductase inhibitor now under development by the Pfizer, Inc., pharmaceutical house). These drugs are inhibitors of the enzyme aldose reductase. After one-year on the appropriate regimens, rats will be sacrificed and their retinal vascular beds will be prepared for microscopic evaluation by trypsin digestion. Using statistical analysis and masking technique to prevent observer bias, we will evaluate the retinal vessels of control animals and those in various experimental groups to determine the presence of abnormalities that may be relevant to diabetes.